NDA Accepted for Narcolepsy Oxybate TRN-257, Gene Therapy ETX101 Early Promise in Dravet, Bexicaserin's Impact on Developmental Encephalopathies

WATCH TIME: 4 minutes

Welcome to this special edition of Neurology News Network. I'm Marco Meglio.

According to a new announcement, the FDA has accepted Tris Pharma’s new drug application (NDA) for TRN-257 for the treatment of cataplexy or excessive daytime sleepiness in adults with narcolepsy, as well as excessive daytime sleepiness in adults with idiopathic hypersomnia, with a PDUFA date set for June 20, 2026.1 The agent incorporates 2 of the company’s proprietary technology platforms, RaftWorks and LiquiXR, to achieve a controlled-release profile and support a once-nightly, low-sodium dosing regimen. The NDA submission is supported by data from multiple pharmacokinetic and safety studies and incorporates Model-Informed Drug Development-based approaches to showcase the efficacy and safety of TRN-257. According to Tris Pharma, the submission also references the agency's prior safety and efficacy findings for currently marketed oxybate products.

At the 2025 American Epilepsy Society (AES) Annual Meeting, held December 5-9 in Atlanta, Georgia, investigators presented promising preliminary efficacy, safety, and neurodevelopmental data from the phase 1/2 POLARIS program testing ETX101 (Encoded Therapeutics), a one-time gene regulation therapy, in young children with Dravet syndrome (DS). All told, the interim results showed that the agent was well tolerated, with dose-dependent effects on seizure outcomes and substantial impacts on neurodevelopment and cognition, further supporting its continued development. Considered the first clinical data for an investigational, one-time, cell-type selective, gene regulation treatment in DS, the presented research included 19 patients who had received a single dose of ETX101 across 4 dose levels as of November 10, 2025. Safety data were available for all participants (n=19), while efficacy measures (Vineland-3, Bayley-4) were available at Week 16 (n = 10) for dose levels (DL)1–3 and at Week 52 (n = 4) for DL1 and DL2. The median age at dosing was 24 months—an age associated with increasing seizure burden—with participants receiving 2–4 antiseizure medications (ASMs), including fenfluramine in 36.8% of cases.

Newly presented findings from a phase 1/2 open-label expanded access program (EAP) showed that patients with developmental and epileptic encephalopathies (DEEs) experienced consistent, sustained reductions in countable motor seizure frequency for up to two years with investigational bexicaserin (Lundbeck). Alongside a favorable safety and tolerability profile, these results support continued advancement into a larger phase 3 program, currently underway as DEEp. The large-scale EAP included patients with a diagnosis of either Dravet syndrome (DS; n = 3), Lennox-Gastaut syndrome (LGS; n = 14), or other DEE (n = 17) who completed the 12-month, double-blind, PACIFIC trial (NCT05364021). In the 12-month OLE, patients received a 6-mg starting dose of bexicaserin, a highly selective superagonist of the 5-hydroxytryptamine type 2C (5-HT2C) receptor, 3 times a day, including those who had received placebo in the randomized controlled trial (RCT) portion.

For more direct access to expert insight, head to NeurologyLive.com. This has been Neurology News Network. Thanks for watching.